Ectopic nephrogenic rest in the inguinal canal in a 6-month-old girl and a review of published studies.

Ectopic nephrogenic rests in the inguinal canal are rare. Usually discovered incidentally during surgery, these rests should raise the suspicion of an early extrarenal Wilms tumor. The differential diagnosis between the two entities is not only difficult but also essential, since they imply different treatment decisions. We report a rare case of an inguinal ectopic nephrogenic rest found in a 6-month-old girl and discuss the clinicopathological implications of this condition. The patient was admitted for a routine repair of a presumed inguinal hernia; during surgery, a nodular mass was noted in the inguinal canal. Pathological diagnosis confirmed the diagnosis of an extrarenal hyperplastic nephrogenic rest. Five previous cases of ectopic nephrogenic rests originating in the inguinal canal have been reported, all of which were associated with a patent processus vaginalis. In this case, the nephrogenic rest was not associated with a congenital inguinal hernia.

Ectopic nephrogenic rests (ENRs) are extremely rare lesions that may occur in any location between the chest wall and the scrotum. Sometimes confused with early extrarenal Wilms tumors (WTs), ENRs can present difficulties in differential diagnosis, which will have an impact on patient management and affect prognosis. To date, only five cases of ENR located in the inguinal canal have been reported in published studies in pediatrics.1–4 We report the case of an inguinal ENR and discuss the practical diagnostic difficulties that a clinician faces when dealing with an incidentally found nephrogenic rest.

CASE

An apparently healthy 6-month-old girl was admitted for routine repair of a presumed right inguinal hernia. At surgery, a 2.5-cm nodular mass was noted in the inguinal canal close to the internal ring; no hernial sac was found. Complete resection of the mass was accomplished. Grossly the resected specimen measured 2.5×1.5×1.0 cm with a nodular external surface. At dissection, the cut surface of the tumor was whitish and of soft rubbery consistency and showed focal hemorrhage without necrosis. Microscopically, the lesion was composed of cellular nodules; no atypical mitoses or anaplastic elements were observed. These nodules were characterized by the presence of embryonal renal tubules, focal fetal glomeruli, cystic spaces lined by columnar or cuboidal cells, and the presence of nests in papillary structures protruding into the cystic spaces (Figure 1). At the periphery of the lesion, there were clusters of fetal glomeruli, embryonal tubules, small blastemal nests, and psammoma bodies in gradual transition to the cellular nodules without a limiting fibrous capsule (Figures 2a, b). The initial pathologic interpretation indicated a nephrogenic embryonal hyperplastic lesion with features more compatible with those of an extrarenal proliferative nephrogenic rest. The lesion was difficult to distinguish from a favorable histology extrarenal WT. Further diagnostic evaluations including abdominal and renal ultrasonography were negative for primary renal tumor or heterotopic nephrogenic rest in other sites. The chest radiography findings were normal. The final pathological diagnosis concluded it was an extrarenal hyperplastic nephrogenic rest as confirmed by the Nephroblastoma Pathology Panel/International Society of Pediatric Oncology. A pediatric hematologist and oncologist were consulted, a “watchful waiting” approach was adopted, and the patient was closely followed up with a surveillance ultrasound every 6 months. Eighteen months after the surgery, the patient was doing well; her follow-up ultrasound scans were negative without any evidence of local recurrence.

Figure 1

The lesion composed of cystic spaces lined by tubular columnar epithelial cells and nodules composed of blastemal nests and tubules. The nodules surround and protrude into the cystic spaces.

Figure 2

A) WT-1 immunohistochemical expression in the nuclei of the blastemal cells and the fetal glomeruli. No expression of WT-1 in the nuclei of the cells lining the cystic space. B) Strong immunohistochemical expression of cytokeratin 8.18 in the tubules and the faint dotlike detection of the antigen in the blastemal cells.

DISCUSSION

The most common lesions encountered incidentally during surgery in the inguinoscrotal region are ectopic adrenal tissue remnants. The overall incidence of the adrenocortical remnants varies from 1% to 9.3% in children undergoing inguinal operations. These rests present as bright yellow nodules (1–5 mm in diameter), and once recognized should be removed as they may undergo marked hyperplasia or neoplastic changes.5 Less frequently, malignant lesions such as neuroblastoma, rhabdomyosarcoma, or mesothelioma may be found in the inguinal region.1 ENRs have been reported in several locations including the heart, thorax, colon, adrenal gland, and lumbosacral area.6 A location in the inguinal canal is extremely rare; this is only the sixth case of an inguinal ENR reported in the pediatric age group (Table 1). Interestingly, all previous cases of an inguinal ENR reported in published studies have been associated with a patent processus vaginalis. The present case is unique as much as the ENR was not associated with a congenital inguinal hernia. Nephrogenic rests appear to develop from a persisting nephrogenic blastema beyond 36 weeks’ gestation when nephrogenesis ceases, and they consist of blastema, epithelial elements, and variable amounts of stroma. Most ENRs undergo maturation, sclerosis, and spontaneous regression; some remain unchanged in size and composition whereas others may progress toward hyperplastic proliferation. Only a minority of nephrogenic rests will undergo neoplastic transformation into either benign adenomas or WTs (1:100 cases). This malignant transformation is most likely the result of a WT1 (11p) gene mutation. Genetic studies have shown that nephrogenic rests often present many of the same chromosomal defects as a WT, supporting the theory that they are precursor lesions to nephroblastoma.7

Table 1

Clinical data of inguinal ectopic nephrogenic rests in published studies.

Reference	Age	Gender	Presentation	Treatment	Follow-up	Outcome
1	14 months	M	Nonpalpable testis	Excision	6 months	Recurrence (Extra renal Wilms tumor)
2	8 months	M	Nonpalpable testis	Excision	18 months	No recurrence
3	2 months	M	Nonpalpable testis	Excision	--	No recurrence
4	5 days	F	Inguinal hernia	Excision	9 months	No recurrence
5	5 days	F	Inguinal hernia	Excision	40 months	No recurrence
Present case	6 months	F	Inguinal hernia	Excision	24 months	No recurrence

Distinguishing between ENR and extrarenal primary, WTs are essential since these entities imply different prognoses and treatment management. Certain criteria should be fulfilled before a lesion can be regarded as an extrarenal WT. The histologic structure of the lesion should confirm the presence of a primitive blastematous spindle or round cell component and provide evidence of abortive or embryonic tubular or glomeruloid structures. Extrarenal WTs are usually round-shaped, form a fibrous pseudocapsule around the lesion, and show atypical mitoses or anaplasia.7,8 Specifically, a nephrogenic rest resembles a favorable histology WT; no clear pathologic separation of the two is observed. In the present case, the nodular pattern and the gradual transition of resting embryonal clusters to cellular blastemal nodules without a dissecting limiting fibrous capsule leaned more toward ENR. However, the infiltrative margin of the lesion, the considerable blastemal component, and the immunohistochemical detection of skeletal muscle fibers represented features of nephroblastoma. The absence of atypical mitoses or anaplastic elements excluded the diagnosis of an established small WT or an anaplastic nephrogenic rest. In addition, as no “overgrowth” of any component was noted, the lesion was diagnosed as a hyperplastic nephrogenic rest rather than an established tumor.

At present, there is no consensus regarding the optimal therapeutic management of a child with an ENR. If the diagnosis is not clear and an extrarenal WT is suspected, the use of stage III guidelines for chemotherapy and radiotherapy is recommended while some authors suggest hyperplastic nephrogenic rests be treated similarly to stage I WT to decrease the risk for WT development.9 Our experience is consistent with the approach of those who recommend close observation with ultrasound surveillance every 6 months for a 4-year period, without adjuvant chemotherapy.2 Given that an ENR may occur from a position as cranial as the chest wall to as caudal as the scrotum, a concurrent primary nephroblastoma or heterotopic nephrogenic rest should be excluded. The clinical behavior of a nephrogenic rest enlarging in size indicates that the lesion may have the potential for a malignant transformation, and imaging is the key to management of this entity.9 Although contrast-enhanced MRI and CT are considered the best imaging modalities, ultrasonography can detect rests as small as 8 mm in dimension and is the modality of choice for surveillance. Abdominal CT and MRI should follow sonographic detection as part of the workup when a nephrogenic rest is discovered.7 In our case, however, the parents refused to give their consent either to a CT scan because of the ionizing radiation or to MRI since this modality requires sedation. Only one of the reported cases with an ENR in the inguinal region developed an extrarenal WT at the same site during the follow-up period.1 Our patient was asymptomatic at 18 months of follow-up and had negative surveillance imaging studies with no evidence of recurrence. Although rare, ENRs should be included in the differential diagnosis of any nodular mass encountered in the inguinal canal. As no specific guidelines for this entity are available, close surveillance with a long-term follow-up is mandatory.